Demonstration of magnetic resonance Z-spectral imaging for fatty acid characterization of bone marrow at 3 T.

Magnetic resonance Z-spectral imaging (ZSI) has emerged as a new approach to measure fat fraction (FF). However, its feasibility for fat spectral imaging remains to be elucidated. In this study, a single-slice ZSI sequence dedicated to fat spectral imaging was designed, and its capability for fatty acid characterization was investigated on peanut oil samples, a multiple-vial fat-water phantom with varied oil volumes, and vertebral body marrow in healthy volunteers and osteoporosis patients at 3 T. The peanut oil spectrum was also recorded with a 400-MHz NMR spectrometer. A Gaussian-Lorentzian sum model was used to resolve water and six fat signals of the pure oil sample or four fat signals of the fat-water phantom or vertebral bone marrow from Z spectra. Fat peak amplitudes were normalized to the total peak amplitude of water and all fat signals. Normalized fat peak amplitudes and FF were quantified and compared among vials of the fat-water phantom or between healthy volunteers and osteoporosis patients. An unpaired student's t-test and Pearson's correlation were conducted, with p less than 0.05 considered statistically significant. The results showed that the peanut oil spectra measured with the ZSI technique were in line with respective NMR spectra, with amplitudes of the six fat signal peaks significantly correlated between the two methods (y = x + 0.001, r = 0.996, p < 0.001 under a repetition time of 1.6 s; and y = 1.026x - 0.003, r = 0.996, p < 0.001 under a repetition time of 3.1 s). Moreover, ZSI-measured FF exhibited a significant correlation with prepared oil volumes (y = 0.876x + 1.290, r = 0.996, p < 0.001). The osteoporosis patients showed significantly higher normalized fat peak amplitudes and FF in the L4 vertebral body marrow than the healthy volunteers (all p < 0.01). In summary, the designed ZSI sequence is feasible for fatty acid characterization, and has the potential to facilitate the diagnosis and evaluation of diseases associated with fat alterations at 3 T.

Assessment of Osteoporosis at the Lumbar Spine Using Ultrashort Echo Time Magnetization Transfer (UTE-MT) MRI.

BACKGROUND: Bone collagen-matrix contributes to the mechanical properties of bone by imparting tensile strength and elasticity, which can be indirectly quantified by ultrashort echo time magnetization transfer ratio (UTE-MTR) to assess osteoporosis. PURPOSE: To evaluate osteoporosis at the human lumbar spine using UTE-MTR. STUDY TYPE: Prospective. POPULATION: One hundred forty-eight-volunteers (age-range, 50-85; females, N = 90), including 81-normal bone density, 35-osteopenic, and 32-osteoporotic subjects. Ten additional healthy volunteers were recruited to study the intrasession reproducibility of the UTE-MT. FIELD STRENGTH/SEQUENCE: 3T/UTE-MT, short repetition-time adiabatic inversion recovery prepared UTE (STAIR-UTE), and iterative decomposition of water-and-fat with echo-asymmetry and least-squares estimation (IDEAL-IQ). ASSESSMENT: Fracture risk was calculated using Fracture-Risk-Assessment-Tool (FRAX). Region-of-interests (ROIs) were delineated on the trabecular area in the maps of bone-mineral-density, UTE-MTR, collagen-bound water proton-fraction (CBWPF), and bone-marrow fat fraction (BMFF). STATISTICAL TESTS: Linear-regression and Bland-Altman analysis were performed to assess the reproducibility of UTE-MTR measurements in the different scans. UTE-MTR and BMFF were correlated with bone-mineral-density using Pearson's regression and with FRAX scores using nonlinear regression. The abilities of UTE-MTR, CBWPF, and BMFF to discriminate between the three patient subgroups were evaluated using receiver-operator-characteristic (ROC) analysis and area-under-the-curve (AUC). Decision-curve-analysis (DCA) and clinical-impact curves were used to evaluate the value of UTE-MTR in clinical diagnosis. The DeLong test was used to compare the ROC curves. P-value <0.05 was considered statistically significant. RESULTS: Excellent reproducibility was obtained for the UTE-MT measurements. UTE-MTR strongly correlated with bone-mineral-density (r = 0.76) and FRAX scores (r = -0.77). UTE-MTR exhibited higher AUCs (≥0.723) than BMFF, indicating its superior ability to distinguish between the three patient subgroups. The DCA and clinical-impact curves confirmed the diagnostic value of UTE-MTR. UTE-MTR and CBWPF showed similar performance in correlation with bone-mineral-density and cohort classification. DATA CONCLUSION: UTE-MTR strongly correlates with bone-mineral-density and FRAX and shows great potential in distinguishing between normal, osteopenic, and osteoporotic subjects. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Marrow Adipocyte Senescence in the Pathogenesis of Bone Loss.

PURPOSE OF REVIEW: Beyond aging, senescent cells accumulate during multiple pathological conditions, including chemotherapy, radiation, glucocorticoids, obesity, and diabetes, even earlier in life. Therefore, cellular senescence represents a unifying pathogenic mechanism driving skeletal and metabolic disorders. However, whether senescent bone marrow adipocytes (BMAds) are causal in mediating skeletal dysfunction has only recently been evaluated. RECENT FINDINGS: Despite evidence of BMAd senescence following glucocorticoid therapy, additional evidence for BMAd senescence in other conditions has thus far been limited. Because the study of BMAds presents unique challenges making these cells difficult to isolate and image, here we review issues and approaches to overcome such challenges, and present advancements in isolation and histological techniques that may help with the future study of senescent BMAds. Further insights into the roles of BMAd senescence in the pathogenesis of skeletal dysfunction may have important basic science and clinical implications for human physiology and disease.

Fat as a Friend or Foe of the Bone.

PURPOSE OF REVIEW: The objective of this review is to summarize the literature on the prevalence and diagnosis of obesity and its metabolic profile, including bone metabolism, focusing on the main inflammatory and turnover bone mediators that better characterize metabolically healthy obesity phenotype, and to summarize the therapeutic interventions for obesity with their effects on bone health. RECENT FINDINGS: Osteoporosis and fracture risk not only increase with age and menopause but also with metabolic diseases, such as diabetes mellitus. Thus, patients with high BMI may have a higher bone fragility and fracture risk. However, some obese individuals with healthy metabolic profiles seem to be less at risk of bone fracture. Obesity has become an alarming disease with growing prevalence and multiple metabolic comorbidities, resulting in a significant burden on healthcare and increased mortality. The imbalance between increased food ingestion and decreased energy expenditure leads to pathological adipose tissue distribution and function, with increased secretion of proinflammatory markers and harmful consequences for body tissues, including bone tissue. However, some obese individuals seem to have a healthy metabolic profile and may not develop cardiometabolic disease during their lives. This healthy metabolic profile also benefits bone turnover and is associated with lower fracture risk.

Assessing osteoporosis in postmenopausal women: preliminary results using a novel lumbar spine phantom-based MRI scoring method.

OBJECTIVE: To develop a novel magnetic resonance imaging (MRI) phantom for producing F-score (for fat) and W-score (for water) and to evaluate the performance of these scores in assessing osteoporosis and related vertebral fractures. MATERIALS AND METHODS: First, a real-time phantom consisting of oil and water tubes was manufactured. Then, 30 female volunteers (age: 62.3 ± 6.3 years) underwent lumbar spine examination with MRI (using a novel phantom) and dual-energy X-ray absorptiometry (DXA), following ethical approval. MRI phantom-based F-score and W-score were defined by normalizing the vertebral signal intensities (SIs) by the oil and water SIs of the phantom on T1- and T2-weighted images, respectively. The diagnostic performances of the new scores for assessing osteoporosis and vertebral fractures were examined using receiver operating characteristic analysis and compared with DXA-measured areal bone mineral density (DXA-aBMD). RESULTS: The F-score and W-score were greater in the osteoporotic patients (3.93 and 2.29) than the non-osteoporotic subjects (3.05 and 1.79) and achieved AUC values of 0.85 and 0.74 (p < 0.05), respectively, when detecting osteoporosis. Similarly, F-score and W-score had greater values for the fracture patients (3.94 and 2.53) than the non-fracture subjects (3.14 and 1.69) and produced better AUC values (0.90 for W-score and 0.79 for F-score) compared to DXA-aBMD (AUC: 0.27, p < 0.05). In addition, the F-score and W-score had a strong correlation (r = 0.77; p < 0.001). CONCLUSION: A novel real-time lumber spine MRI phantom was developed, based upon which newly defined F-score and W-score were able to detect osteoporosis and demonstrated an improved ability over DXA-aBMD in differentiating patients with vertebral fractures.

Greater bone marrow fat and myosteatosis are associated with lower vBMD but not asymptomatic vertebral fracture.

OBJECTIVES: Organ fat may affect bone metabolism and be associated with vertebral fracture (VF). This study aimed to explore relationships between VF, adiposity indexes measured by MRI, and volumetric BMD (vBMD) measured by quantitative CT (QCT). METHODS: Four hundred volunteers, ranging in age from 22 to 83 years, were recruited and underwent same-day abdominal QCT and chemical shift-encoded (CSE) MRI. We used MRI to quantify the fat content of bone marrow (BMF), psoas major and paraspinal muscles, and the liver. Abdominal fat, VF, and vBMD of the lumbar spine were measured by QCT. For VF discrimination analysis, we examined both the whole cohort (60 VF cases in 30 men and 30 women) and a restricted subgroup of those aged over 50 years (50 VF cases in 23 men and 27 women). RESULTS: Amongst the men, a 1 SD increase in BMF was associated with a 27.67 (95% CI, -32.71 to -22.62) mg/cm3 decrease in vBMD after adjusting for age and BMI. Amongst women, all adiposity indexes except for liver fat were significantly associated with vBMD, with BMF having the strongest association (ß, -24.00; 95% CI, -28.54 to -19.46 mg/cm3). Similar findings were also observed in participants aged over 50 years. The associations of adiposity indexes with vertebral fracture were not significant after adjusting for age in both sexes aged over 50 years. CONCLUSIONS: In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. However, marrow fat and other adipose tissues were not associated with radiographic-based prevalent vertebral fractures. KEY POINTS: • In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. • Among women, all adiposity indexes except for liver fat content were significantly associated with vBMD, with bone marrow fat having the strongest association. • Marrow fat and other adipose tissues were not associated with radiographic-based asymptomatic vertebral fractures.

Differences in specific abdominal fat depots between metabolically healthy and unhealthy children with overweight/obesity: The role of cardiorespiratory fitness.

OBJECTIVES: Fat depots localization has a critical role in the metabolic health status of adults. Nevertheless, whether that is also the case in children remains under-studied. Therefore, the aims of this study were: (i) to examine the differences between metabolically healthy (MHO) and unhealthy (MUO) overweight/obesity phenotypes on specific abdominal fat depots, and (ii) to further explore whether cardiorespiratory fitness plays a major role in the differences between metabolic phenotypes among children with overweight/obesity. METHODS: A total of 114 children with overweight/obesity (10.6 ± 1.1 years, 62 girls) were included. Children were classified as MHO (n = 68) or MUO. visceral (VAT), abdominal subcutaneous (ASAT), intermuscular abdominal (IMAAT), psoas, hepatic, pancreatic, and lumbar bone marrow adipose tissues were measured by magnetic resonance imaging. Cardiorespiratory fitness was assessed using the 20 m shuttle run test. RESULTS: MHO children had lower VAT and ASAT contents and psoas fat fraction compared to MUO children (difference = 12.4%-25.8%, all p < 0.035). MUO-unfit had more VAT and ASAT content than those MUO-fit and MHO-fit (difference = 34.8%-45.3%, all p < 0.044). MUO-unfit shows also greater IMAAT fat fraction than those MUO-fit and MHO-fit peers (difference = 16.4%-13.9% respectively, all p ≤ 0.001). In addition, MHO-unfit presented higher IMAAT fat fraction than MHO-fit (difference = 13.4%, p < 0.001). MUO-unfit presented higher psoas fat fraction than MHO-fit (difference = 29.1%, p = 0.008). CONCLUSIONS: VAT together with ASAT and psoas fat fraction, were lower in MHO than in MUO children. Further, we also observed that being fit, regardless of metabolic phenotype, has a protective role over the specific abdominal fat depots among children with overweight/obesity.

People living with HIV have low trabecular bone mineral density, high bone marrow adiposity, and poor trabecular bone microarchitecture at the proximal femur.

People living with HIV (PLWH) have increased risk of osteoporosis and fractures. We assessed the proximal femur of PLWH and age-matched seronegative controls using quantitative computed tomography and magnetic resonance imaging. Results suggest that the trabecular compartment is compromised at fracture-prone regions in the proximal femur of PLWH. INTRODUCTION: People living with HIV (PLWH) have increased risk of osteoporosis and fractures. However, studies assessing the main determinants of bone strength in the proximal femur exclude this vulnerable population. We assessed the proximal femur of 40 PLWH and 26 age-matched seronegative controls using quantitative computed tomography and magnetic resonance imaging. METHODS: We examined cortical volumetric bone mineral density (Ct.vBMD), trabecular vBMD (Tb.vBMD), cortical thickness (Ct.Th), bone marrow adiposity (BMA), and trabecular number, separation, and bone volume fraction. Parametric comparisons between the two groups were made for the femoral head, femoral neck, trochanter, and total hip using linear regression adjusting for several covariates, including metrics of body composition. In addition, we investigated the associations of BMA with Tb.vBMD and trabecular microarchitecture with Spearman's rank partial correlations. RESULTS: PLWH had lower Tb.vBMD and deteriorated trabecular microarchitecture in the femoral neck, trochanter and total hip, and elevated BMA in the femoral head, femoral neck, and total hip. Ct.vBMD and Ct.Th were not significantly different between the two groups. BMA was significantly associated with lower Tb.vBMD and deteriorated trabecular microarchitecture in both groups albeit at different femoral regions. CONCLUSIONS: Our findings suggest that the trabecular, and not the cortical, compartment is compromised in the proximal femur of PLWH. The observed impairments in fracture-prone regions in PLWH indicate lower femoral strength and suggest higher fracture risk. The inverse associations of BMA with trabecular bone density and microarchitecture quality agree with findings at other anatomic sites and in other populations, suggesting that excess BMA possibly due to a switch from the osteoblast to the adipocyte lineage may be implicated in the pathogenesis of bone fragility at the femur in PLWH.

Q-Dixon and GRAPPATINI T2 Mapping Parameters: A Whole Spinal Assessment of the Relationship Between Osteoporosis and Intervertebral Disc Degeneration.

BACKGROUND: The relationship between osteoporosis and intervertebral disc (IVD) degeneration remains controversial. Novel quantitative Dixon (Q-Dixon) and GRAPPATINI T2 mapping techniques have shown potential for evaluating the biochemical components of the spine. PURPOSE: To investigate the correlation of osteoporosis with IVD degeneration in postmenopausal women. STUDY TYPE: Prospective. SUBJECTS: A total of 105 postmenopausal females (mean age, 65 years; mean body mass index, 26 kg/m2 ). FIELD STRENGTH/SEQUENCE: 3 T; sagittal; 6-echo Q-Dixon, multiecho spin-echo GRAPPATINI T2 mapping, turbo spin echo (TSE) T1-weighted and TSE T2-weighted sequences. ASSESSMENT: The subjects were divided into normal (N = 47), osteopenia (N = 28), and osteoporosis (N = 30) groups according to quantitative computed tomography examination. The Pfirrmann grade of each IVD was obtained. Region of interest analysis was performed separately by two radiologists (X.L., with 10 years of experience, and S.C., with 20 years of experience) on a fat fraction map and T2 map to calculate the bone marrow fat fraction (BMFF) from the L1 to L5 vertebrae and the T2 values of each adjacent IVD separately. STATISTICAL TESTS: One-way analysis of variance, post-hoc comparisons, and Kruskal-Wallis H tests were performed to evaluate the differences in the magnetic resonance imaging parameters between the groups. The relationships between BMFF and the IVD features were analyzed using the Spearman correlation analysis and linear regression models. RESULTS: There were significant differences in BMFF among the three groups. The osteoporosis group had higher BMFF values (64.5 ± 5.9%). No significant correlation was found between BMFF and Pfirrmann grade (r = 0.251, P = 0.06). BMFF was significantly negatively correlated with the T2 of the adjacent IVD from L1 to L3 (r = -0.731; r = -0.637; r = -0.547), while significant weak correlations were found at the L4 to L5 levels (r = -0.337; r = -0.278). DATA CONCLUSION: This study demonstrated that osteoporosis is associated with IVD degeneration. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 4.

Quantifying Bone Marrow Fat Fraction and Iron by MRI for Distinguishing Aplastic Anemia from Myelodysplastic Syndromes.

BACKGROUND: Bone marrow of patients with aplastic anemia (AA) is different from that of patients with myelodysplastic syndrome (MDS) and is difficult to identify by blood examination. IDEAL-IQ (iterative decomposition of water and fat with echo asymmetry and least-squares estimation) imaging might be able to quantify fat fraction (FF) and iron content in bone tissues. PURPOSE: To determine if IDEAL-IQ measurements of bone marrow FF and iron content can distinguish between patients with AA and MDS. STUDY TYPE: Retrospective. POPULATION: Fifty-seven patients with AA, 21 patients with MDS, and 24 healthy controls. FIELD STRENGTH/SEQUENCE: 3.0 T, IDEAL-IQ sequence. ASSESSMENT: Three independent observers evaluated the IDEAL-IQ images and measured FF and R2* in the left posterior superior iliac spine. STATISTICAL TESTS: Kruskal-Wallis test, linear correlations, and Bland-Altman analysis were used. A P-value of <0.05 was considered statistically significant. RESULTS: The FF in patients with AA (79.46% ± 15.00%) was significantly higher than that in patients with MDS (42.78% ± 30.09%) and control subjects (65.50% ± 14.73%). However, there was no significant difference in FF between control subjects and patients with MDS (P = 0.439). The R2* value of AA, MDS, and controls was 145.38 ± 53.33, (171.13 ± 100.89, and 135.99 ± 32.41/second, respectively, with no significant difference between the three groups (P = 0.553). DATA CONCLUSION: Quantitative IDEAL-IQ magnetic resonance imaging may facilitate the diagnosis of AA and distinguish it from MDS. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Marrow Fat Content and Composition in ß-Thalassemia: A Study using 1 H-MRS.

BACKGROUND: ß-thalassemia is a genetic disease that causes abnormal production of red blood cells (ineffective erythropoiesis, IE). IE is a condition known to change bone marrow composition. PURPOSE: To evaluate the effect of IE on the marrow fat content and fat unsaturation levels in the proximal femur using 1 H-MRS. STUDY TYPE: Prospective. SUBJECTS: Twenty-three subjects were included in this study, seven control and 16 ß-thalassemia subjects. FIELD STRENGTH/SEQUENCE: 3.0T; stimulated echo acquisition Mode (STEAM); magnetic resonance spectroscopy (MRS) sequence. ASSESSMENT: Multiecho MRS scans were performed in four regions of the proximal left femur of each subject, that is, diaphysis, femoral neck, femoral head, and greater trochanter. The examined regions were grouped into red (diaphysis and femoral neck) and yellow marrow regions (femoral head and greater trochanter). STATISTICAL TESTS: The Jonckheere-Terpstra test was used to evaluate the impact of increasing disease severity on bone marrow fat fraction (BMFF), marrow conversion index, and fat unsaturation index (UI). Pairwise comparison analysis was performed when a significant trend (P < 0.05) was found. K-means clustering analysis was used to examine the clusters observed when BMFF in the red and yellow regions were studied (diaphysis against greater trochanter). RESULTS: BMFF showed a significant decreasing trend with increasing disease severity in both red (TJT = 109.00, z = -4.414, P < 0.05) and yellow marrow regions (TJT = 108.00, z = -4.438, P < 0.05). The opposite trend was observed in UI in both bone marrow regions (red marrow: TJT = 180.5, z = 3.515, P < 0.05; yellow marrow: TJT = 155.0, z = 2.282, P = 0.05). Three distinct forms of marrow adipogenesis were found when plotting BMFF diaphysis against BMFF greater trochanter: 1) normal (centroid: 80.4%, 66.6%), 2) partial disruption (centroid: 51.1%, 16.6%), and 3) total disruption (centroid: 2.6%, 1.6%). DATA CONCLUSION: ß-thalassemia is associated with decreased marrow fat, and increased marrow fat unsaturation level. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

MRI Assessment of Bone Marrow Composition in Osteoporosis.

PURPOSE OF REVIEW: To provide an overview on recent technical development for quantifying marrow composition using magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques, as well as a summary on recent findings of interrelationship between marrow adipose tissue (MAT) and skeletal health in the context of osteoporosis. RECENT FINDINGS: There have been significant technical advances in reliable quantification of marrow composition using MR techniques. Cross-sectional studies have demonstrated a negative correlation between MAT and bone, with trabecular bone associating more strongly with MAT than cortical bone. However, longitudinal studies of MAT and bone are limited. MAT contents and composition have been associated with prevalent vertebral fracture. The evidence between MAT and clinical fracture is more limited, and, to date, no studies have reported on the relationship between MAT and incident fracture. Increasing evidence suggests a dynamic role of marrow fat in skeletal health. Reliable non-invasive quantification of marrow composition will facilitate developing novel treatment strategies for osteoporosis.

Pathogenesis of Osteoporosis.

Osteoporosis is a condition where bone resorption exceeds bone formation leading to degeneration. With an aging population, the prevalence of osteoporosis is on the rise. Although advances in the field have made progress in targeting the mechanisms of the disease, the efficacy of current treatments remains limited and is complicated by unexpected side effects. Therefore, to overcome this treatment gap, new approaches are needed to identify and elucidate the cellular mechanisms mediating the pathogenesis of osteoporosis, which requires a strong understanding of bone biology. This chapter will focus on bone cells (osteoclasts, osteoblasts, and osteocytes) and their role in the bone turnover process in normal physiology and in pathology. With regard to osteoclast function, the regulators and underpinning signaling pathways leading to bone resorption will be discussed. Decreased osteoblastogenesis also contributes to bone deterioration with aging and osteoporosis; hence the factors and signaling pathways mediating osteoblast formation and function will be examined. Osteocytes are mature osteoblasts embedded in bone matrix and act as endocrine cells; their role in bone health and pathology will also be reviewed. In addition, this chapter will explore the emerging role of adipocytes in bone biology and the implications of increased bone marrow fat infiltration with aging on bone degeneration. In conclusion, a greater understanding of the pathogenesis of osteoporosis is of utmost importance in order to develop more effective treatments for osteoporosis and other bone diseases.

Intervertebral disc degeneration associated with vertebral marrow fat, assessed using quantitative magnetic resonance imaging.

OBJECTIVE: To investigate the potential clinical application of quantitative MRI in assessing the correlation between lumbar vertebrae bone marrow fat deposition and intervertebral disc degeneration. MATERIALS AND METHODS: A total of 104 chronic lower-back pain volunteers underwent 3.0-T MRI with T2-weighted imaging, T2 mapping, and iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL-IQ) between August 2018 and June 2019. Each disc was assessed with T2 value by T2 mapping, and the L1-S1 vertebral bone marrow fat fraction was assessed by IDEAL-IQ. The differences and relationship between T2 value and the adjacent vertebral bone marrow fat fraction values within the five Pfirrmann groups, five age groups, and five lumbar levels were statistically analyzed. RESULTS: The vertebral bone marrow fat fraction had a significant negative correlation with T2 values of nucleus pulposus' T2 values (p < 0.001). However, the significant negative correlation was only found between T2 values of nucleus pulposus and adjacent vertebral bone marrow fat in Pfirrmann II-III, L1/2-L5/S1 level, and 40-49 years' age groups. Pfirrmann grades of the intervertebral disc were positively correlated with adjacent vertebrae bone marrow fat fraction (p < 0.05). CONCLUSION: Lumbar bone marrow fat deposition significantly increases during the early stages of intervertebral disc degeneration. Quantitative measurements of bone marrow fat deposition and water content of intervertebral discs have a predictive value and are an important supplement to the qualitative traditional classification strategies for the early stages of intervertebral disc degeneration.

Associations between vertebral body fat fraction and intervertebral disc biochemical composition as assessed by quantitative MRI.

BACKGROUND: There is an interplay between the intervertebral disc (IVD) and the adjacent bone marrow that may play a role in the development of IVD degeneration and might influence chronic lower back pain (CLBP). PURPOSE: To apply novel quantitative MRI techniques to assess the relationship between vertebral bone marrow fat (BMF) and biochemical changes in the adjacent IVD. STUDY TYPE: Prospective. SUBJECTS: Forty-six subjects (26 female and 20 male) with a mean age of 47.3 ± 12.0 years. FIELD STRENGTH/SEQUENCE: 3 T MRI; a combined T1ρ and T2 mapping pulse sequence and a 3D spoiled gradient recalled sequence with six echoes and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) reconstruction algorithm. ASSESSMENT: Using quantitative MRI, the vertebral BMF fraction was measured as well as the biochemical composition (proteoglycan and collagen content) of the IVD. Furthermore, clinical Pfirrmann grading, Oswestry disability index (ODI), and visual analog scale (VAS) was assessed. STATISTICAL TESTS: Mixed random effects models accounting for multiple measurements per subject were used to assess the relationships between disc measurements and BMF. RESULTS: The relationships between BMF (mean) and T1ρ /T2 (mean and SD) were significant, with P < 0.05. Significant associations (P < 0.001) were found between clinical scores (Pfirrmann, ODI, and VAS) with T1ρ /T2 (mean and SD). BMF mean was significantly related to ODI (P = 0.037) and VAS (P = 0.043), but not with Pfirrmann (P = 0.451). In contrast, BMF SD was significantly related to Pfirrmann (P = 0.000) but not to ODI (P = 0.064) and VAS (P = 0.13). DATA CONCLUSION: Our study demonstrates significant associations between BMF and biochemical changes in the adjacent IVD, both assessed by quantitative MRI; this may suggest that the conversion of hematopoietic bone marrow to fatty bone marrow impairs the supply of available nutrients to cells in the IVD and may thereby accelerate disc degeneration. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:1219-1226.

The Regulation of Marrow Fat by Vitamin D: Molecular Mechanisms and Clinical Implications.

PURPOSE OF REVIEW: To review the available literature regarding a possible relationship between vitamin D and bone marrow adipose tissue (BMAT), and to identify future avenues of research that warrant attention. RECENT FINDINGS: Results from in vivo animal and human studies all support the hypothesis that vitamin D can suppress BMAT expansion. This is achieved by antagonizing adipogenesis in bone marrow stromal cells, through inhibition of PPARγ2 activity and stimulation of pro-osteogenic Wnt signalling. However, our understanding of the functions of BMAT is still evolving, and studies on the role of vitamin D in modulating BMAT function are lacking. In addition, many diseases and chronic conditions are associated with low vitamin D status and low bone mineral density (BMD), but BMAT expansion has not been studied in these patient populations. Vitamin D suppresses BMAT expansion, but its role in modulating BMAT function is poorly understood.

Marrow Fat-Secreted Factors as Biomarkers for Osteoporosis.

PURPOSE OF REVIEW: The age-related accumulation of bone marrow adipose tissue (BMAT) negatively impacts bone metabolism and hematopoiesis. This review provides an overview about BMAT-secreted factors as biomarkers for BMAT accumulation and osteoporosis risk. RECENT FINDINGS: The adipokines leptin and adiponectin are regulators of BMAT. It remains to be clarified if locally produced adipokines substantially contribute to their peripheral serum levels and if they influence bone metabolism beyond that of extraosseous adipokine production. Existing data also suggests that BMAT disturbs bone metabolism primarily through palmitate-mediated toxic effects on osteoblasts and osteocytes, including dysregulated autophagy and apoptosis. BMAT-secreted factors are important modulators of bone metabolism. However, the majority of our understanding about MAT-secreted factors and their paracrine and endocrine effects is derived from in vitro studies and animal experiments. Therefore, more research is needed before BMAT-secreted biomarkers can be applied in medical practice.

Peripheral Neuropathy as a Component of Skeletal Disease in Diabetes.

PURPOSE OF REVIEW: The goal of this review is to explore clinical associations between peripheral neuropathy and diabetic bone disease and to discuss how nerve dysfunction may contribute to dysregulation of bone metabolism, reduced bone quality, and fracture risk. RECENT FINDINGS: Diabetic neuropathy can decrease peripheral sensation (sensory neuropathy), impair motor coordination (motor neuropathy), and increase postural hypotension (autonomic neuropathy). Together, this can impair overall balance and increase the risk for falls and fractures. In addition, the peripheral nervous system has the potential to regulate bone metabolism directly through the action of local neurotransmitters on bone cells and indirectly through neuroregulation of the skeletal vascular supply. This review critically evaluates existing evidence for diabetic peripheral neuropathy as a risk factor or direct actor on bone disease. In addition, we address therapeutic and experimental considerations to guide patient care and future research evaluating the emerging relationship between diabetic neuropathy and bone health.

Vertebral bone marrow fat content in normal adults with varying bone densities at 3T magnetic resonance imaging.

BACKGROUND: Sex-related differences of vertebral bone marrow fat in relation to varying bone densities have not yet been evaluated although some studies have reported an inverse association of bone marrow fat and bone mineral density (BMD). PURPOSE: To evaluate the relationship between bone marrow fat and BMD and to demonstrate the sex-related differences of the vertebral bone marrow fat in normal adults with varying bone densities. MATERIAL AND METHODS: A total of 123 normal adult volunteers were enrolled in this study. 1H-MRS of the lumbar spine was performed. The fat fraction (FF) values of vertebral bone marrow were measured. Volumetric BMD measurement was performed by quantitative computed tomography (QCT). All participants were divided into three groups according to BMD (normal, osteopenia, osteoporosis). The differences in the FF and body mass index (BMI) values of the three groups were compared, and partial correlation analysis was used to evaluate the correlation between FF values and BMD/BMI. RESULTS: The FF values increased with decreasing BMD in both male and female participants. There were significant sex differences for the FF values in the normal bone density group ( P < 0.001). The FF values of the normal bone density group in male participants were significantly higher than those of the female participants ( P < 0.001). The FF values were significantly negative correlated with BMD for all participants (r = -0.820, P < 0.001). CONCLUSION: The FF values of vertebral bone marrow correlated inversely with BMD. Sex-related differences of FF values was related to BMD.

Bone marrow adipocytes support hematopoietic stem cell survival.

In bone marrow (BM), hematopoietic elements are mingled with adipocytes (BM-A), which are the most abundant stromal component in the niche. BM-A progressively increase with aging, eventually occupying up to 50% of BM cavities. In this work, the role played by BM-A was explored by studying primary human BM-A isolated from hip surgery patients at the molecular level, through microarray analysis, and at the functional level, by assessing their relationship with primary human hematopoietic stem cells (HSC) by the long-term culture initiating cell (LTC-IC) assay. Findings demonstrated that BM-A are capable of supporting HSC survival in the LTC-IC assay, since after 5 weeks of co-culture, HSC were still able to proliferate and differentiate. Furthermore, critical molecules such as C-X-C motif chemokine 12 (CXCL12), interleukin (IL)-8, colony-stimulating factor 3 (CSF3), and leukaemia inhibitory factor (LIF), were expressed at similar levels in BM-A and in primary human BM mesenchymal stromal cells (BM-MSC), whereas IL-3 was higher in BM-A. Interestingly, BM-A displayed a different gene expression profile compared with subcutaneous adipose tissue adipocytes (AT-A) collected from abdominal surgery patients, especially in terms of regulation of lipid metabolism, stemness genes, and white-to-brown differentiation pathways. Accordingly, analysis of the gene pathways involved in hematopoiesis regulation showed that BM-A are more closely related to BM-MSC than to AT-A. The present data suggest that BM-A play a supporting role in the hematopoietic niche and directly sustain HSC survival.